“This is the first example of taking a genetic sequence and designing a drug candidate that works effectively in an animal model against
triple-negative breast cancer,” said Matthew Disney, a TSRI professor. “The study represents a clear breakthrough in precision medicine, as this
molecule only kills the cancer cells that express the cancer-causing gene, not healthy cells. These studies may transform the way the lead drugs are
identified—by using the genetic makeup of a disease.”

In the study, Disney’s lab demonstrates
how their compound Targaprimir-96 precisely targets the cells that cause the cancer and triggers them to kill themselves by programmed cell death. The lab
conducted 21-day courses of treatment on animal models. The results showed marked decrease in production of microRNA and increased programmed cell death,
which significantly reduced tumor growth. Targaprimir-96 was shown to be highly selective in its targeting, as healthy cells remained unaffected.

The study uses a new approach, which they’ve called called Informa, to develop designer compounds to bind to RNA
folds, specifically microRNAs, which bind to the transcript of one or more genes and act as a sort of “dimmer switch” to prevent the production
of protein. In some cases, microRNAs have been associated with the development of disease and have been known to slow the programmed cell death that
mitigates the excessive cell growth that causes cancer.

The Informa approach could eliminate the extremely time-
consuming and expensive screening procedure currently used to find the few drugs out of millions of candidates that would be most effective against the
disease-causing molecules. This tactic may transform how drugs are identified by using the genetic signature of the specific cells targeted, allowing for
quicker and more effective treatment for cancer patients.

Disney noted that typically therapeutic drugs for cancer
cells tend to kill indiscriminately, causing side effects for patients that can be hard to tolerate. In an interview with DDNews, he admitted there
is a lot of work ahead. “We hope that in the future these studies are not just one drug but a suite of drugs to target a variety of cancer-causing gene
products,” he stated. “Hopefully we are just seeing the tip of the iceberg and that these studies get to patients as soon as they can, but a lot
of work remains.”

“In the future, we hope to apply this strategy to target other disease-causing RNAs,
which range from incurable cancers to important viral pathogens such as Zika and Ebola,” added Sai Pradeep Velagapudi, a TSRI research associate in the
Disney lab and the first author of the study.

In addition to Disney and Velagapudi, authors of the study,
“Design of a Small Molecule Against an Oncogenic Non-coding RNA,” were Michael D. Cameron, Christopher L. Haga, Laura H. Rosenberg, Marie
Lafitte, Derek Duckett and Donald G. Phinney.

The work was supported by the National Institutes of Health and The
Nelson Fund for Therapeutic Development.

In other recent cancer research news from TSRI, scientists at the
institute’s California campus have identified a protein that launches cancer growth and appears to contribute to higher mortality in breast cancer
patients, which may indicate a promising new target for drug discovery in oncology. The new findings, published June 27, 2016 in the journal Nature
Structural & Molecular Biology, suggest that future therapies might target the protein GlyRS to halt cancer growth. The research revealed that GlyRS
is actually a sort of “double agent” in that it serves a biologically essential role in making proteins, but it also can help to further modify
proteins in a way that launches cancer growth. Look for more on that research in the August issue of DDNews.